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Modern drug delivery applications of chitosan
Advanced Drug Delivery Reviews 52 (2001) 103 www.elsevier.com / locate / drugdeliv
Preface
Modern drug delivery applications of chitosan This present issue of Advanced Drug Delivery Reviews focuses on the role of chitosan, and chitosan derivatives in modern drug delivery. Chitosan is a polysaccharide derived by deacetylation of chitin, a by-product of the seafood industry. Chitosan meets the important requirements for excipients in drug delivery, namely biocompatibility and biodegradability. Due to these favourable properties, the interest in chitosan and its derivatives as excipients in drug delivery has increased in recent years [1,2]. Successively, chitosan has been investigated as mucoadhesive polymer [3], and as a permeation enhancer for drug delivery in vitro [4] and at mucosal epithelia [5,6]. In this respect, chitosan is able to open epithelial tight junctions to allow for an increase in paracellular transport of macromolecular drugs. Other properties of chitosan, such as the interaction of chitosan with the immune system, and its role in the wound healing process is described by Ueno et al. in the first chapter of this issue. Chitosan, however, suffers from low solubility at a physiological pH of 7.4, limiting its use as absorption enhancer in, for example, nasal or peroral delivery systems. To overcome this problem, a number of cationic or anionic chitosan derivatives have been synthesized and tested. A summary of these studies is given by Thanou et al. in the second chapter. Another approach to increase the bioavailability of macromolecular drugs is to inhibit enzymatic degradation at the site of absorption. Chitosan itself does not inhibit intestinal enzymes such as trypsin or chymotrypsin. However, by covalent attachment of enzyme inhibitors to the chitosan backbone, enzyme degradation of the drug to be delivered might be prevented. This approach is described in Chapter 3, ¨ written by Bernkopp-Schnurch and Kast. Chitosan and chitosan derivatives easily form
micro- and nanoparticles, which are being investigated as delivery systems for vaccines in mucosal immunization studies, and plasmid DNA in non-viral gene therapy. These two fields of increasing importance are reviewed in the last two chapters, written by van der Lubben et al. and Borchard. The present issue, covering diverse topics of modern drug delivery, is supposed to give an overview over what is known, and what is to be expected from this peculiar polymer. References [1] L. Illum, Chitosan and its use as a pharmaceutical excipient, Pharm. Res. 15 (1998) 1326–1361. [2] V. Dodane, V.D. Vilivalam, Pharmaceutical applications of chitosan, Pharm. Sci. Technol. Today 1 (1998) 246–253. [3] C.-M. Lehr, J.A. Bouwstra, E.H. Schacht, H.E. Junginger, In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers, Int. J. Pharm. 78 (1992) 43– 48. [4] P. Artursson, T. Lindmark, S.S. Davis, L. Illum, Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2), Pharm. Res. 11 (1994) 1358–1361. [5] H.L. Lueßen, B.J. de Leeuw, M.W. Langemeyer, A.G. de Boer, J.C. Verhoef, H.E. Junginger, mucoadhesive polymers in peroral peptide drug delivery. VI. Carbomer and chitosan improve the intestinal absorption of the peptide buserelin in vivo, Pharm. Res. 13 (1996) 1668–1672. [6] L. Illum, N.F. Farraj, S.S. Davis, Chitosan as a novel nasal delivery system for peptide drugs, Pharm. Res. 11 (1994) 1186–1189.
Gerrit Borchard Hans E. Junginger (Theme Editors)
Leiden /Amsterdam Center for Drug Research Division of Pharmaceutical Technology Leiden University P.O. Box 9502, 2300 RA Leiden The Netherlands
0169-409X / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0169-409X( 01 )00188-0
E-mail: [email protected]
Preface
Modern drug delivery applications of chitosan This present issue of Advanced Drug Delivery Reviews focuses on the role of chitosan, and chitosan derivatives in modern drug delivery. Chitosan is a polysaccharide derived by deacetylation of chitin, a by-product of the seafood industry. Chitosan meets the important requirements for excipients in drug delivery, namely biocompatibility and biodegradability. Due to these favourable properties, the interest in chitosan and its derivatives as excipients in drug delivery has increased in recent years [1,2]. Successively, chitosan has been investigated as mucoadhesive polymer [3], and as a permeation enhancer for drug delivery in vitro [4] and at mucosal epithelia [5,6]. In this respect, chitosan is able to open epithelial tight junctions to allow for an increase in paracellular transport of macromolecular drugs. Other properties of chitosan, such as the interaction of chitosan with the immune system, and its role in the wound healing process is described by Ueno et al. in the first chapter of this issue. Chitosan, however, suffers from low solubility at a physiological pH of 7.4, limiting its use as absorption enhancer in, for example, nasal or peroral delivery systems. To overcome this problem, a number of cationic or anionic chitosan derivatives have been synthesized and tested. A summary of these studies is given by Thanou et al. in the second chapter. Another approach to increase the bioavailability of macromolecular drugs is to inhibit enzymatic degradation at the site of absorption. Chitosan itself does not inhibit intestinal enzymes such as trypsin or chymotrypsin. However, by covalent attachment of enzyme inhibitors to the chitosan backbone, enzyme degradation of the drug to be delivered might be prevented. This approach is described in Chapter 3, ¨ written by Bernkopp-Schnurch and Kast. Chitosan and chitosan derivatives easily form
micro- and nanoparticles, which are being investigated as delivery systems for vaccines in mucosal immunization studies, and plasmid DNA in non-viral gene therapy. These two fields of increasing importance are reviewed in the last two chapters, written by van der Lubben et al. and Borchard. The present issue, covering diverse topics of modern drug delivery, is supposed to give an overview over what is known, and what is to be expected from this peculiar polymer. References [1] L. Illum, Chitosan and its use as a pharmaceutical excipient, Pharm. Res. 15 (1998) 1326–1361. [2] V. Dodane, V.D. Vilivalam, Pharmaceutical applications of chitosan, Pharm. Sci. Technol. Today 1 (1998) 246–253. [3] C.-M. Lehr, J.A. Bouwstra, E.H. Schacht, H.E. Junginger, In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers, Int. J. Pharm. 78 (1992) 43– 48. [4] P. Artursson, T. Lindmark, S.S. Davis, L. Illum, Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2), Pharm. Res. 11 (1994) 1358–1361. [5] H.L. Lueßen, B.J. de Leeuw, M.W. Langemeyer, A.G. de Boer, J.C. Verhoef, H.E. Junginger, mucoadhesive polymers in peroral peptide drug delivery. VI. Carbomer and chitosan improve the intestinal absorption of the peptide buserelin in vivo, Pharm. Res. 13 (1996) 1668–1672. [6] L. Illum, N.F. Farraj, S.S. Davis, Chitosan as a novel nasal delivery system for peptide drugs, Pharm. Res. 11 (1994) 1186–1189.
Gerrit Borchard Hans E. Junginger (Theme Editors)
Leiden /Amsterdam Center for Drug Research Division of Pharmaceutical Technology Leiden University P.O. Box 9502, 2300 RA Leiden The Netherlands
0169-409X / 01 / $ – see front matter 2001 Elsevier Science B.V. All rights reserved. PII: S0169-409X( 01 )00188-0
E-mail: [email protected]